Purpose: The purpose of this study was to explore the effects of implant angulation and its possible influence on prosthetic connection as regards implant/tooth strains in a combined implant and natural tooth abutment fixed partial denture. Methods: A natural tooth was embedded between vertically-aligned and 17 angulated implants in a polymethyl methacrylate acrylic resin model. Three designs (Group 1: tooth and vertically-aligned implant; Group 2: tooth and 17 angulated implant, Group 3: tooth and vertically-aligned implant having a different prosthetic connection to Group 1) of tooth-implant supported prostheses (n = 4) were fabricated. Strain gauges were bonded on the prostheses and on the approximal sides of the natural tooth abutment and implants. Once the test fixed partial dentures were seated, a static load of 150 N was applied to each prosthesis. During testing, strain-gauge signals were digitalized by a data acquisition system and this signal was stored and assessed with corresponding software at a sample rate of 10 KHz. Results: The data were then evaluated using Mann-Whitney U and Kruskal Wallis tests at 95% confidence level. Mesiodistal tilting of implants increased peri-implant strains in implant-tooth supported prostheses during torque-tightening and under load. The mode of prosthesis connection may affect strains within the prosthesis and natural tooth abutments, although its impact under static loading conditions seems negligible. Conclusions: This investigation suggests that mesiodistal tilting of implants may have a biomechanical effect in tooth-implant supported prostheses.